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rdf:type |
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lifeskim:mentions |
umls-concept:C0017725,
umls-concept:C0030012,
umls-concept:C0035820,
umls-concept:C0215848,
umls-concept:C0871261,
umls-concept:C0871712,
umls-concept:C0947647,
umls-concept:C1326912,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1822686,
umls-concept:C2348110,
umls-concept:C2348977,
umls-concept:C2911692
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pubmed:issue |
2
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pubmed:dateCreated |
2002-1-22
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pubmed:abstractText |
We have investigated the role of HIF-1 in the cellular response to redox modulation via the inhibition of oxidative phosphorylation. We demonstrate that manipulation of redox in air, achieved by inhibiting cytochrome oxidase with cyanide, induces HIF-1 mediated transcription in wild-type CHO and HT1080 human tumour cells but not in CHO cells deficient in the oxygen responsive, HIF-1alpha sub-unit of HIF-1. Hypoglycaemia attenuates cyanide-mediated transcription in non-transformed HIF-1 wild-type CHO cells but not the human tumour derived cell line. Cells lacking either HIF-1alpha, or the second composite sub-unit of HIF-1, HIF-1beta, were markedly more sensitive to the combined stress of perturbed redox and hypoglycaemia than wild-type cells. As such conditions together with hypoxia are prevalent in tumours, these data suggest that HIF-1 may have a protective role in adaptation to the tumour micro-environment. In support of this we demonstrate that HIF-1alpha deficient cells are less tumorigenic than wild-type cells. They showed a reduced growth rate when grown as xenografts in nude mice. This was not related to vascular parameters that were identical to those found in HIF-1 wild-type tumours. The HIF-1 deficient tumours lacked focal expression of Glut-1 in hypoxic tumour regions. Compromised glucose uptake and metabolic adaptation to the tumour micro-environment may form the basis of the reduced tumorigenicity associated with these cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharide Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLC2A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
282-90
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11803471-Animals,
pubmed-meshheading:11803471-CHO Cells,
pubmed-meshheading:11803471-Cell Survival,
pubmed-meshheading:11803471-Cell Transformation, Neoplastic,
pubmed-meshheading:11803471-Cricetinae,
pubmed-meshheading:11803471-DNA-Binding Proteins,
pubmed-meshheading:11803471-Female,
pubmed-meshheading:11803471-Fibrosarcoma,
pubmed-meshheading:11803471-Glucose,
pubmed-meshheading:11803471-Glucose Transporter Type 1,
pubmed-meshheading:11803471-Humans,
pubmed-meshheading:11803471-Hypoglycemia,
pubmed-meshheading:11803471-Hypoxia-Inducible Factor 1,
pubmed-meshheading:11803471-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11803471-Mice,
pubmed-meshheading:11803471-Mice, Nude,
pubmed-meshheading:11803471-Monosaccharide Transport Proteins,
pubmed-meshheading:11803471-Mutagenesis,
pubmed-meshheading:11803471-Neovascularization, Pathologic,
pubmed-meshheading:11803471-Nuclear Proteins,
pubmed-meshheading:11803471-Oxidation-Reduction,
pubmed-meshheading:11803471-Transcription Factors,
pubmed-meshheading:11803471-Transplantation, Heterologous,
pubmed-meshheading:11803471-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
A protective role for HIF-1 in response to redox manipulation and glucose deprivation: implications for tumorigenesis.
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pubmed:affiliation |
School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester, M13 9PL, UK. kaye.williams@man.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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